Specific tetraspanin functions

Abstract

Relatively little attention has been given to the large family of abundantly expressed transmembrane proteins known as tetraspanins. Now, the importance of tetraspanins is strongly supported by emerging genetic evidence, coupled with new insights into the biochemistry and functions of tetraspanin protein complexes.

Figure 1.

The mammalian tetraspanin family. 27 human and 1 murine protein sequences were clustered using the CLUSTALW program. *Accession number; no other names are available. **Murine sequence. Shaded tetraspanins are those that are mutated in humans, and/or deleted in mice (see text for details).

Figure 2.

Key residues present in most tetraspanins. The percentage conservation at each of the indicated 26 amino acid positions is derived from an alignment of 28 distinct human tetraspanins (Fig. 1), together with 37 Drosophila tetraspanins (Todres et al., 2000). Notably, uroplakins 1a and 1b, peripherin, and ROM contain as many of these conserved residues (15–18 amino acids) as do the so-called “true” tetraspanins CD9 and CD81. Thus they also should be considered as “true” tetraspanins. Many proteins (such as connexins, CD20, sarcospan, and claudins) contain four transmembrane domains, but are not tetraspanins because they lack all or nearly all of the conserved tetraspanin residues indicated here. Despite their names, TM4SF1, TM4SF4, and TM4SF5 also lack all or nearly all of the conserved residues indicated here, and should not be considered as members of the tetraspanin family (Wright et al., 2000).